Artemis plays a crucial role in the hairpin‐opening step of antigen receptor VDJ gene recombination in the presence of catalytic subunit of deoxyribonucleic acid (DNA)‐dependent protein kinase ...(DNA‐PKcs). A defect in Artemis causes human radiosensitive‐severe combined immunodeficiency. Cells from Artemis‐deficient patients and mice display increased chromosomal instability, but the precise function of this factor in the response to DNA damage remains to be elucidate. In this study, we show that Artemis is hyperphosphorylated in an Ataxia‐telangiectasia‐mutated (ATM)‐ and Nijmegen breakage syndrome 1 (Nbs1)‐dependent manner in response to ionizing radiation (IR), and that S645 is an SQ/TQ site that contributes to retarded mobility of Artemis upon IR. The hyperphosphorylation of Artemis is markedly reduced in ATM‐ and Nbs1‐null cells. Reintroduction of wild‐type ATM or Nbs1 reconstituted Artemis hyperphosphorylation in ATM‐ or Nbs1‐deficient cells, respectively. In support of this functional link, hyperphosphorylated Artemis was found to physically associate with the Mre11/Rad50/Nbs1 complex in an ATM‐dependent manner in response to IR‐induced DNA double strand breaks (DSB). Since deficiency of either DNA‐Pkcs or ATM leads to defective repair of IR‐induced DSB, our finding places Artemis at the signaling crossroads downstream of DNA‐PKcs and ATM in IR‐induced DSB repair. (Cancer Sci 2005; 96: 134–141)
Differentiation is a highly regulated process whereby cells become specialized to perform specific functions and lose the ability to perform others. In contrast, the question of whether ...dedifferentiation is a genetically determined process, or merely an unregulated loss of the differentiated state, has not been resolved. We show here that dedifferentiation in the social amoeba Dictyostelium discoideum relies on a sequence of events that is independent of the original developmental state and involves the coordinated expression of a specific set of genes. A defect in one of these genes, the histidine kinase dhkA, alters the kinetics of dedifferentiation and uncouples the progression of dedifferentiation events. These observations establish dedifferentiation as a genetically determined process and suggest the existence of a developmental checkpoint that ensures a return path to the undifferentiated state.
It is well known that the retention of porphyrins might be the cause of secondary porphyria cutanea tarda (PCT) in uremic patients. In recent years, however, the prevalence of PCT in uremic patients ...has decreased partly due to the use of high-performance dialysis membranes, as well as to the administration of recombinant erythropoietin. Previously, we reported that high-performance dialysis membranes efficiently remove porphyrins in hemodialyzed patients. In the present study, we measured plasma porphyrin concentrations by HPLC analysis and examined the correlation between porphyrin concentration and red blood cell count parameters during the correction of renal anemia in hemodialyzed patients. In eight anuric maintenance hemodialyzed patients examined for 12 months, changes in plasma coproporphyrin concentrations negatively correlated with MCHC changes, suggesting the utilization of porphyrin during erythropoiesis. However, six patients newly introduced to hemodialysis were examined during the first month of treatment; changes in their plasma coproporphyrin concentrations positively correlated with RBC, Hb, and Ht. The reason for the latter results might be ascribed to the concomitant improvement in nutritional conditions favoring the production of porphyrin. The results obtained in the present study suggest that the measurement of plasma porphyrin levels may be useful in the clinical evaluation of the treatment of renal anemia in hemodialyzed patients.
Standard reference ranges for all laboratory test values are mandatory. This study was designed to establish a reference range for blood vitamin B1 levels, since the normal range has not been ...determined in the Japanese population. We founded the Japan Committee for Vitamin Laboratory Standards, which was incorporated with the Vitamin Society of Japan and the Japanese Society of Nutrition and Food Science. We standardized whole blood vitamin B1 levels using three HPLC techniques (post‐column reverse‐phase HPLC, pre‐column reverse‐phase HPLC, and precolumn GP‐HPLC). The reference range was obtained in 54 volunteers administered a 1,800 kcal diet with 2 mg of vitamin B1 (1.74 mg measured) daily to avoid marginal vitamin B1 deficiency in the population. The range for each assay was 26—47, 28—51, and 28—56 ng/ml, respectively. Our data suggest that 26—28 ng/ml is the lower limit of normal for whole blood vitamin B1, but further studies in a larger population are needed in order to obtain more definitive results.
: Omenn syndrome is a variant form of severe combined immunodeficiency. It is fatal unless treated by allogeneic stem cell transplantation (SCT), which is the only curative approach. However, both ...treatment‐related complications and graft rejection are major obstacles to treatment success. This report describes a case with Omenn syndrome who developed mixed chimerism after unrelated cord blood transplantation (UCBT). This case was successfully treated by altering the patient's immunosuppression and donor lymphocyte infusion (DLI) with donor cord blood‐derived activated CD4+ T cells ex vivo expanded from the cord blood cell residues in an infused bag. This novel development to expand CD4+ T‐lymphocytes from the donor cord blood unit for the use of DLI would serve as a useful method to overcome the risk of graft rejection in SCT for primary immunodeficiency disorders with residual cell‐mediated immunity without compounding graft‐vs.‐host disease, especially in the UCBT setting.
Dictyostelium is a favored model for studying problems in cell and developmental biology. To comprehend the genetic potential and networks that direct growth and multicellular development, we are ...performing a large‐scale analysis of Dictyostelium cDNAs. Here, we newly determine 7720 nucleotide sequences of cDNAs from the multicellular, slug stage (S) and 10 439 from the unicellular, vegetative stage (V). The combined 26 954 redundant ESTs were computer assembled using the PHRAP program to yield 5381 independent sequences. These 5381 predicted genes represent about half of the estimated coding potential of the organism. One‐third of them were classified into 12 functional categories. Although the overall classification patterns of the V and S libraries were very similar, stage‐specific genes exist in every category. The majority of V‐specific genes function in some aspect of protein translation, while such genes are in a minority in the S‐specific and common populations. Instead, genes for signal transduction and multicellular organization are enriched in the population of S‐specific genes. Genes encoding the enzymes of basic metabolism are mainly found in the common gene population. These results therefore suggest major differences between growing and developing Dictyostelium cells in the nature of the genes transcribed.
Abstract
Standard reference ranges for all laboratory test values are mandatory. This study was designed to establish a reference range for blood vitamin B
1
levels, since the normal range has not ...been determined in the Japanese population. We founded the Japan Committee for Vitamin Laboratory Standards, which was incorporated with the Vitamin Society of Japan and the Japanese Society of Nutrition and Food Science. We standardized whole blood vitamin B
1
levels using three HPLC techniques (post‐column reverse‐phase HPLC, pre‐column reverse‐phase HPLC, and precolumn GP‐HPLC). The reference range was obtained in 54 volunteers administered a 1,800 kcal diet with 2 mg of vitamin B
1
(1.74 mg measured) daily to avoid marginal vitamin B
1
deficiency in the population. The range for each assay was 26—47, 28—51, and 28—56 ng/ml, respectively. Our data suggest that 26—28 ng/ml is the lower limit of normal for whole blood vitamin B
1
, but further studies in a larger population are needed in order to obtain more definitive results.
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